The Tox21 programs federal partners include NIH, with leadership from NCATS and the National Toxicology Program (NTP) at the National Institute of Environmental Health Sciences (NIEHS), the Environmental Protection Agency (EPA), and the Food and Drug Administration (FDA). These agencies work together to advance in vitro toxicological testing. The Tox21 program is comprised of the following specialties: Computational Toxicology, Systems Toxicology and Genomic Toxicology. The Tox21 Computational Toxicology team has enhanced a variety of tools that are routinely used by Tox21 partners to access each others data. The team performed data analysis of more than 18 assays that were identified, developed, optimized and/or screened by the Tox21 Systems Toxicology team and gene expression data generated by the Tox21 Genomic Toxicology team. These activities include normalization and correction, fitting of concentration-response curves to generate potency and efficacy measures, classification of curves based on a set of criteria that included significance of fit (measured by p-values), completeness of fit and efficacy, evaluation of assay performance by data reproducibility, data-driven selection of compounds for follow up studies, and identification of genes and pathways involved in cell responses to chemical exposure. The Tox21 Computational Toxicology team also has updated the PubChem deposition tool to facilitate the deposition of the Tox21 10K triplicate screen data into PubChem. The 10K data from all assays screened up to FY 2015 have been made public in PubChem totaling 100 assay entries (AIDs) and over 55 million data points. The Tox21 Computational Toxicology team also has completed the Tox21 Data Challenge 2014, a crowdsourcing competition that developed computational models based on the 10K data from 12 pathway assays, including assays from both the nuclear receptor signaling panel and the stress response pathway panel. The Challenge was launched on July 16, 2014, and closed for scoring on November 14, 2014. The winners were announced on January 26, 2015. One hundred twenty-five participants registered for the Challenge representing 18 different countries. Three hundred seventy-eight model submissions from 40 teams were received for final evaluation. The winning models all achieved >80 percent accuracy, with several models exceeding 90 percent accuracy. The winning models will be made publicly available to the scientific community to aid in compound prioritization. A special issue in Frontiers in Environmental Science has been dedicated to the Tox21 Challenge to publish articles from the Challenge participants. The Tox21 data repository and browser, including the online assay tracking system, have been updated to facilitate data sharing and assay annotations. The Tox21 Computational Toxicology team has been working with the Tox21 chemical working group to generate PDF files for the Tox21 10K library chemical QC results. These results have been released in the public Tox21 Data Browser, and the links to the PDFs have been provided for Tox21 compounds deposited in PubChem. Furthermore, a new Web-based browser has been developed for the NCATS BioPlanet database. This development will allow the Tox21 program to collect a list of all human pathways and design assays that can measure their chemical responses. BioPlanet will annotate the nearly 2,000 unique human pathways by source, species, biological function and process, disease and toxicity relevance, and availability of probing assays. Manual curation of pathway annotations is continuing. This tool will be made available to the Tox21 partners and the public in due course.